Rv0648 Resolved · high auto-curated
H37Rv Rv0648 · MTBC0 - ·
1215 aa · 742719–746366 (+) ·
RefSeq NP_215162.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alpha-mannosidase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Alpha-mannosidase. Pfam: Glyco_hydro_38N (PF01074.29), Alpha-mann_mid (PF09261.17), NPCBM_assoc (PF10633.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P96937
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | Alpha-mannosidase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| eggNOG description | alpha-mannosidase |
| Orthologous group | COG0383 |
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.621 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 15 missense, 2 nonsense, 2 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 1.11% of strains (1615) · convergent |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Glyco_hydro_38N | PF01074.29 | 2.5e-36 | 2–211 | Glycosyl hydrolases family 38 N-terminal domain |
Alpha-mann_mid | PF09261.17 | 1.4e-13 | 216–304 | Alpha mannosidase middle domain |
NPCBM_assoc | PF10633.16 | 2.1e-19 | 1008–1082 | NPCBM-associated, NEW3 domain of alpha-galactosidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0650 (sugar kinase), high confidence from genomic context alone (score 959 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0650 |
sugar kinase | 963 | 959 ctx | neighborhood:801 coexpression:745 |
Rv0649 fabD2 |
malonyl CoA-acyl carrier protein transacylase | 959 | 959 ctx | neighborhood:802 coexpression:802 |
Rv0745 hyp |
hypothetical protein | 793 | 793 | coexpression:793 |
Rv0620 galK |
galactokinase | 735 | 735 | coexpression:735 |
Rv1999c |
transporter | 734 | 733 | coexpression:733 |
Rv0371c hyp |
hypothetical protein | 731 | 731 | coexpression:731 |
Rv0601c |
two component sensor kinase HK2 | 691 | 692 | coexpression:692 |
Rv0048c |
membrane protein | 648 | 648 ctx | cooccurence:648 |
Rv0646c lipG |
lipase/esterase LipG | 615 | 615 ctx | neighborhood:552 |
Rv0647c hyp |
hypothetical protein | 586 | 585 ctx | neighborhood:558 |
Rv1635c |
mannosyltransferase | 544 | 544 ctx | cooccurence:544 |
Rv3446c hyp |
hypothetical protein | 534 | 535 | coexpression:425 |
Rv1904 hyp |
hypothetical protein | 512 | 513 ctx | cooccurence:510 |
Rv3271c |
integral membrane protein | 510 | 510 | coexpression:411 |
Rv0188 |
transmembrane protein | 505 | 506 ctx | cooccurence:499 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): alpha-mannosidase
- Pfam (hmmscan --cut_ga): Glyco_hydro_38N PF01074.29 (E=3e-36), Alpha-mann_mid PF09261.17 (E=1e-13), NPCBM_assoc PF10633.16 (E=2e-19)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215162.1)
- Domains: Pfam-A via hmmscan --cut_ga — Glyco_hydro_38N (PF01074.29), Alpha-mann_mid (PF09261.17), NPCBM_assoc (PF10633.16)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0383 - Curated reference: UniProt P96937 (TrEMBL, unreviewed; Inferred from homology)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
39 functional partner(s); context anchor
Rv0650 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0648| MMGGTYNEPNTNLTSPETTIRNLVHGIGFQRDVLGAEPATAWQLDVFGHDPQFPGLAADAGLTSSSWARGPHHQWGPAQGGVDRMQFCSEFEWIAPSGRGLLTHYMPAHYSAGWSMDSSTSLADAEAATYALFDQLKKVALTRNVLLPVGTDYTPPNKWVTAIHRDWGARYTWPRFVCALPKEFFAAVRAELAKRGWVPSPQTRDMNPIYTGKDVSYIDTKQANRAAENAVLEAERFAVFAALLTGAEYPQAALAKAWVQLAYGAHHDAITGSESDQVYLDLLTGWRDAWELGRAARDNSLRLLSGAVAASHDRVVVWNPLTQRRTDIVTARVDPPLQAGVRVFDPDGAEVAALVEHDGRSVTWLACDVPSLGWRVYRLVPADEAPGWELVPGTDIANEHYRLAVDPERGGALSSLVQDGRQLIAAGRVANELALYEEYPSHPTQGEGPWHLLPTGPVVCSSACPAQVQAYRGPLGQRLVVRGRIGTLLRYTQTLTLWDGVDRVDCRTSIDEFTGEDRLLRLRWPCPVPGAMPISEVGDAVVGRGFALLHEGPESVDTAQHPWTLDNPAYGWFGLSSAVRVRAGDGVRAVSVAEVVSPTETVSGPMARDLMVALVRAGVTATCSGADKPRYGHLDVDSNLPDARIALGGPDRNTFTKAVLAEAAPAYTAELQRQLAKTGTARVWVPAANPLARAWLPGADLRAPCALPVLVIDGRDEKHLRAAVASLADDLADAEIVVHQRAAPQMEPFEDRTVALLNRGVPSFAVDSEGTLHTALMRSCTGWPSGVWIDQPRRTAPDGSNFQLQHWTHHFDYALVCGGGDWRRAGIPARSAQFSHPLLAVAPRRPQGELPAVGSLLHVEPADSVQLGALKAAGNPLAAGSARPVQPAAVALRLVQTTGADTPVTIGCELGKVGALRPADLLETPLAMARARKSSIDLHGYQVATVLARLDVAADMANVLAADDVALAPHAETAQPQYARYWLHNRGPAPLGGLPAVAHLHPRRVRGQPGDDVVLRLTAASDCTDSVLGGVVDVVCPLGWPATPARLPFTLGAGAHLQADIALSIPAGAPPGPYPVRAQLRVVDTAVPAAWRQVVEDVCVVTVGADSDLEELVYLVDGPADIELAAGDRARLAVTIGSRAHAELALDAHSISPWGTWEWIGPPALGAVLPARGMAKLAFDVTPPAWLEPGQWWALVRVGCAGQLVYSPAVKVSVT